Departments of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Prev Res (Phila). 2022 Apr 1;15(4):217-223. doi: 10.1158/1940-6207.CAPR-21-0066.
Why celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP.
This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP. See related Spotlight, p. 205.
为什么塞来昔布仅在某些家族性腺瘤性息肉病 (FAP) 患者中发挥化学预防作用仍知之甚少。我们进行了一项 II 期临床研究，以确定 FAP 中塞来昔布化学预防活性的潜在预测生物标志物。27 例 FAP 患者完成了为期 6 个月的口服 400mg 塞来昔布，每日两次；在塞来昔布治疗前后进行结肠镜检查，以评估结直肠息肉瘤负担，并获得正常和息肉结直肠活检，以通过 LC/MS-MS 测量塞来昔布、13-S-羟基十八碳二烯酸 (13-HODE)、15-HETE、12-HETE 和 LTB4 水平。还测量了这些患者治疗前和治疗后 2、4 和 6 个月时血清中的塞来昔布水平。27 例患者中有 19 例对塞来昔布有反应，根据结肠镜检查结果的可重复定量评估，结直肠息肉负担减少了≥28%。息肉组织中的塞来昔布水平明显低于正常结直肠组织。在对塞来昔布有反应的患者中，血清和正常结直肠组织中的塞来昔布水平呈正相关，但在无反应的患者中无相关性。在测量的脂氧合酶产物中，只有 13-HODE 水平在息肉组织中明显低于正常组织。我们的研究结果表明，塞来昔布在正常组织和息肉组织之间的生物利用度存在差异，以及其对 FAP 患者临床反应的潜在影响。
本研究评估了 FAP 患者塞来昔布化学预防活性的潜在预测生物标志物。我们的研究结果表明，塞来昔布在正常组织和息肉组织之间的生物利用度存在差异，以及其对 FAP 患者临床化学预防反应的潜在影响。见相关焦点文章，第 205 页。
